Ion transfer tubes are well-known in the mass spectrometry art for transporting ions from an ionization chamber, which typically operates at or near atmospheric pressure, to a region of reduced pressure. Generally described, an ion transfer tube typically consists of a narrow elongated conduit having an inlet end open to the ionization chamber, and an outlet end open to the reduced-pressure region. Ions formed in the ionization chamber (e.g., via an electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI) process), together with partially desolvated droplets and background gas, enter the inlet end of the ion transfer tube, traverse its length under the influence of the pressure gradient, and exit the outlet end into a lower-pressure chamber—namely, the first vacuum stage of a mass spectrometer. The ions subsequently pass through apertures in one or more partitions, such apertures possibly in skimmer cones, through regions of successively lower pressures and are thereafter delivered to a mass analyzer for acquisition of a mass spectrum.
FIG. 1 is a simplified schematic diagram of a general conventional mass spectrometer system comprising an atmospheric pressure ionization (API) source coupled to an analyzing region via an ion transfer tube. Referring to FIG. 1, an API source 12 housed in an ionization chamber 14 is connected to receive a liquid sample from an associated apparatus such as for instance a liquid chromatograph or syringe pump through a capillary 7. The API source 12 optionally is an electrospray ionization (ESI) source, a heated electrospray ionization (H-ESI) source, an atmospheric pressure chemical ionization (APCI) source, an atmospheric pressure matrix assisted laser desorption (MALDI) source, a photoionization source, or a source employing any other ionization technique that operates at pressures substantially above the operating pressure of mass analyzer 28 (e.g., from about 1 torr to about 2000 torr). Furthermore, the term API source is intended to include a “multi-mode” source combining a plurality of the above-mentioned source types. The API source 12 forms charged particles 9 (either ions or charged droplets that may be desolvated so as to release ions) representative of the sample, which charged particles are subsequently transported from the API source 12 to the mass analyzer 28 in high-vacuum chamber 26 through at least one intermediate-vacuum chamber 18. In particular, the droplets or ions are entrained in a background gas and transported from the API source 12 through an ion transfer tube 16 that passes through a first partition element or wall 11 into an intermediate-vacuum chamber 18 which is maintained at a lower pressure than the pressure of the ionization chamber 14 but at a higher pressure than the pressure of the high-vacuum chamber 26. The ion transfer tube 16 may be physically coupled to a heating element or block 23 that provides heat to the gas and entrained particles in the ion transfer tube so as to aid in desolvation of charged droplets so as to thereby release free ions.
Due to the differences in pressure between the ionization chamber 14 and the intermediate-vacuum chamber 18 (FIG. 1), gases and entrained ions are caused to flow through ion transfer tube 16 into the intermediate-vacuum chamber 18. A plate or second partition element or wall 15 separates the intermediate-vacuum chamber 18 from either the high-vacuum chamber 26 or possibly a second intermediate-pressure region (not shown), which is maintained at a pressure that is lower than that of chamber 18 but higher than that of high-vacuum chamber 26. Ion optical assembly or ion lens 20 provides an electric field that guides and focuses the ion stream leaving ion transfer tube 16 through an aperture 22 in the second partition element or wall 15 that may be an aperture of a skimmer 21. A second ion optical assembly or lens 24 may be provided so as to transfer or guide ions to the mass analyzer 28. The ion optical assemblies or lenses 20, 24 may comprise transfer elements, such as, for instance a multipole ion guide, so as to direct the ions through aperture 22 and into the mass analyzer 28. The mass analyzer 28 comprises one or more detectors 30 whose output can be displayed as a mass spectrum. Vacuum port 13 is used for evacuation of the intermediate-vacuum chamber and vacuum port 19 is used for evacuation of the high-vacuum chamber 26.
FIG. 2 is a schematic illustration of a portion, in particular, an outlet portion 50 of a known ion transfer tube. The upper and lower parts of FIG. 2 respectively show a cross-sectional view and a perspective view of the outlet portion 50. The ion transfer tube comprises a tube 52 (in this example, cylindrical tube) having a hollow interior or bore 54, the flow direction through which is indicated by the dashed arrow. At the outlet end 51 of the ion transfer tube, the tube 52 is terminated by a substantially flat end surface 56 that is substantially perpendicular to the length of the tube and to the flow direction. Further, a beveled surface or chamfer 58, which in the case of the cylindrical tube shown is a frustoconical surface, is disposed at an angle to the end surface so as to intersect both the end surface 56 and the outer cylindrical surface of the tube 52. The surface 58 may be used to align and seat outlet end of the ion transfer tube against a mating structural element (not shown) in the interior of the intermediate vacuum chamber 18 or may be used so as to penetrate, upon insertion into a mass spectrometer instrument, a vacuum sealing element or valve, such as the sealing ball disclosed in U.S. Pat. No. 6,667,474, in the names of Abramson et al., said patent incorporated by reference herein in its entirety.
Generally, there is a differential pressure of 750 to 760 Torr across the length of the ion transfer tube (e.g., ion tube 16 of FIG. 1), which leads to an expansion at the outlet end. This expansion is characterized by a rapid increase of the velocity of the ionized analyte containing gas that flows into the first vacuum stage of the mass spectrometer. Under some configurations, the expanding plume may even become supersonic and shockwaves may occur within the lower pressure chamber. It is to be appreciated that this expansion may lead to less-than-optimal conditions to transfer ions across the vacuum interface, and could for instance lead to a suppression of certain ions based on their charge state.
The number of ions delivered to the mass analyzer (as measured by peak intensities or total ion count) is partially governed by the flow rate through the ion transfer tube. It is generally desirable to provide relatively high flow rates through the ion transfer tube so as to deliver greater numbers of ions to the mass analyzer and achieve high instrument sensitivity. Although the flow rate through the ion transfer tube may be increased by enlarging the tube bore (inner diameter), such enlargement of the ion transfer tube diameter results in an increased gas load that, in the absence of increased pumping capacity, causes the pressures in the vacuum chambers to increase as well. Since it is necessary to maintain the mass analyzer and detector region under high vacuum conditions, the increase in pressure must be counteracted by increasing the number of vacuum pumps employed and/or increasing the pumping capacity of the vacuum pumps. Of course, increasing the number and/or capacity of the vacuum pumps also increases the cost of the mass spectrometer, as well as the power requirements, shipping weight and cost, and bench space requirements. Thus, for practical reasons, the inner diameter of an ion transfer tube is relatively small, on the order of 500 microns.
The forced flow of background gas and entrained ionized analyte through a small diameter ion transfer tube may cause a significant increase in velocity of the background gas and analyte. In some configurations, in which the ion transfer tube is short (approaching a simple aperture) and possibly shaped as a de Laval nozzle, the flow may become supersonic upon exiting the outlet end of the ion transfer tube. More generally, however, viscous drag against the tube interior will maintain the flow within the tube, and possibly exiting the tune, at sub-sonic velocities. Under such conditions, the Reynolds number, Re, for fluid flow in a pipe may apply, where this dimensionless quantity is defined as:
  Re  =            ρ      ⁢                          ⁢      vL        η  in which ρ is density (kg/m3), ν is the velocity (m/s), L is a characteristic length and η is the fluid viscosity (Pa-s).
Because of the low cross-sectional area of the ion transfer tube and expected high flow rates within the tube the flow regime in the tube may, the Reynolds number for flow within the tube may correspond to a transition flow regime (neither fully-laminar nor fully-turbulent) and the Reynolds number for the expanding plume exiting the tube may correspond to either transition or turbulent flow. Unfortunately, this non-laminar and possibly turbulent flow exiting the ion transfer tube often results in many of the ions failing to flow into downstream apertures and chambers of the device. Moreover, ions which follow the resulting off-line trajectories within the intermediate-vacuum chamber may encounter curved fringing electric fields from various ion optical elements in the apparatus. Ions with lower mass-to-charge ratio (m/z) may be expected to be more susceptible to trajectory-bending effects of such fields, thereby resulting in (m/z)-selective ion loss.
On a more practical matter, to manufacture these ion transfer tubes with a well defined length, a de-burring step must be performed. This step leads to small irreproducible differences between capillary specimens. The inventors have experimentally observed that these surface variations lead to (m/z)-dependent varying detected abundances of ions, and possibly even increased fragmentation of fragile ions such as peptides. The inventors have further experimentally determined that the use of an ion transfer tube in accordance with the present invention provides enhanced detected abundances of some ions whose relative proportions or absolute abundances are otherwise under-represented when a conventional ion transfer tube is employed. Even a specially made perfectly square tube end does not lead to a detected abundance of these ions that is comparable to that of the present invention, which employs a cylindrical tube interior having at least one diameter change.
It is thus hypothesized that the geometry or spread of turbulent or otherwise disturbed or perturbed flow at the outlet end of an ion transfer tube may be highly dependent upon small variations of viscous drag related to minor shape variations or to the presence of sharp corners, surface roughness or other irregularities at the outlet end of the ion transfer tube. The hypothesized resulting variable and uncontrolled flow exiting the conventional ion transfer tube may then lead to dispersal of ions away from a nominal instrumental trajectory thereby leading to either actual physical loss from the instrumental system or, possibly, fragmentation of fragile ions upon encountering regions of high RF voltage. Providing a special tool to produce exact replicas that avoid such variations would lead to an expected increase in manufacturing costs.
Regardless of the exact causes, the above-noted effects of decreased transmission efficiency, selective ion loss, and possibly ion fragmentation appear to have not been previously recognized, as it appears that transmission efficiency variations related to outlet-end variations of the ion transfer tube have generally been at least partially counteracted, in practice, by adjustment of the placement of the tube or ion optic elements, variation of chamber pressure, or other operating parameters. However, not all apparatus configurations may admit such adjustments. There is thus a need for an ion transfer tube geometry that can provide high ion transmission efficiency and that can be easily and cost-effectively reproducibly manufactured. The instant teachings provide a solution to this important problem.